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LYSOSOMAL ACID
LIPASE DEFICIENCY
TESTING
What is lysosomal acid lipase
deficiency?
Lysosomal acid lipase (LAL) deficiency is a rare,
inherited condition that affects the body’s
ability to break down fats and cholesterol
(lipids). It results in the buildup of very large
amounts of lipids inside organs and tissues
throughout the body.
LAL deficiency can occur in infants, children, adolescents,
and adults. The type that occurs during infancy is called
Wolman disease. Shortly after birth, infants with Wolman
disease may develop some of the following signs and
symptoms1-3:
•• Swelling or bloating of the abdomen (abdominal
distention)
•• Liver and spleen enlargement
•• Yellowing of the skin and eyes (jaundice)
•• Calcium deposits on the adrenal glands
•• Forceful vomiting, frequent diarrhea, and foul smelling,
fatty stools
•• Failure to gain weight and grow
•• Inability to absorb nutrients from food (malnutrition)
There is no treatment for this condition. Infants with
Wolman disease often die within the first year of life.1-3
The type of LAL deficiency that occurs in children,
adolescents, and adults is called cholesteryl ester storage
disease (CESD).
•• CESD progresses more slowly than Wolman disease,
may cause mild symptoms or no symptoms at all, and
may go undiagnosed until later in life.1,4
•• It can lead to liver inflammation and damage
(cirrhosis), liver failure, and early death.1,4,5 It may also
cause an increased risk for early-onset heart disease
due to the buildup of lipids inside the walls of
blood vessels.1,6
•• It may be managed with a low-fat (cholesterol
and triglycerides) diet and cholesterol-lowering
medications, but the disorder can not be cured. If liver
failure occurs, liver transplantation may be an option.1,4
Enzyme replacement therapy is currently being
researched as another possible treatment for CESD.1,5
What causes LAL deficiency?
LAL deficiency is caused by abnormal changes in a gene.
Genes are found in every cell in your body. They carry the
instructions for making proteins that control how each of
your cells work. Genes can undergo abnormal changes
(called mutations) that may cause cells to stop working
the way they should. Gene mutations may result in
health problems, and they may be passed from parent to
child (inherited).
The LIPA gene contains instructions for making lysosomal
acid lipase, a protein that helps cells break down lipids so
they can be used by the body and carried to the liver for
removal. When the LIPA gene is altered, cells may make
little or no LAL, or the LAL that is made will not work
properly. This keeps the body from using lipids properly
and causes very large amounts of lipids to build up inside
organs and tissues.
How is LAL deficiency inherited?
Normally, each of your cells carries 2 copies of all your
genes. You inherit 1 copy of a gene from each of your
parents. LAL deficiency disorder is inherited in an
autosomal recessive manner.1,3,4 This means a child must
inherit 2 copies of a LIPA mutation (1 copy from each
parent) in order to be affected with LAL deficiency.
People who carry 1 LIPA mutation are not affected
with LAL deficiency. However, when 2 people who are
carriers of LIPA mutations have children, there is a 1 in
4 (25%) chance with each pregnancy that the child will
inherit both copies of the mutation and be affected with
LAL deficiency.
How is LAL deficiency diagnosed?
Diagnosing LAL deficiency begins with a physical exam,
medical history, and laboratory tests, such as cholesterol
testing and liver function tests. A blood test that detects
LYSOSOMAL ACID LIPIDASE DEFICIENCY | GENETIC TESTING
low or absent levels of the LAL enzyme may be used to
confirm a diagnosis of LAL deficiency.3,4,6
LIPA full gene sequencing is a procedure that reads the
instructions (DNA) that make up the LIPA gene. This is
a way to identify the presence of altered LIPA genes in a
person’s cells, helping a doctor confirm the diagnosis of
LAL deficiency. The test can be performed on a sample
of blood or prenatal samples of amniotic fluid (the watery
substance that surrounds a fetus) or the chorionic villi (a
small piece of tissue taken from the placenta).3
What possible results of enzyme testing can be
reported, and what might they mean?
•• Unaffected: The enzyme level falls within the
unaffected range. This result would rule out a
diagnosis of LAL deficiency.
•• Affected: The enzyme level is absent or low enough
to indicate an affected individual. This result would
confirm a diagnosis of LAL deficiency.
•• Intermediate: The enzyme level falls between the
affected and unaffected ranges. The interpretation of
this result may vary depending on the enzyme level
and available clinical information.
Test results should be combined with clinical findings
and reviewed by a heath professional who specializes in
medical genetics.
Where can I find more information?
If you have questions or want more information about
testing for LAL deficiency, ask your doctor or genetic
counselor. You may search for a genetic counselor in
your area using an online address book provided by the
National Society of Genetic Counselors at www.nsgc.org.
Other information resources include:
Where can I find more information?
•• Genetics Home Reference
Home page: http://ghr.nlm.nih.gov
Note: This material is provided for general information purposes only. It is not intended as a
substitute for medical advice and/or consultation with a physician or technical expert.
References
1. Assmann G, Seedorf U. Acid lipase deficiency: Wolman disease and cholesteryl ester storage disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B, eds. The Metabolic and Molecular Basis
of Inherited Disease. Vol 3. 8th ed. New York, NY: McGraw-Hill; 2001:3551-3572.
2. US National Library of Medicine. Wolman disease. Genetics Home Reference Web site. http://ghr.nlm.nih.gov/condition/wolman-disease. Accessed April 10, 2013.
3. National Organization of Rare Diseases. Wolman disease. http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1213/viewAbstract. Accessed April 10, 2013.
4. National Organization of Rare Diseases. Cholesteryl ester storage disease. http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1214/viewAbstract. Accessed April 15, 2013.
5. Du H, Schiavi S, Levine M, Mishra J, Heur M, Grabowski GA. Enzyme therapy for lysosomal acid lipase deficiency in the mouse. Molecular Human Genetics. 201;10(16):1639-1648.
6. Hamilton, J., Jones, I., Srivastava, R. and Galloway, P. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clinica Chimica Acta. 2012;413:1207-1210.
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